11-[4-{2-(2-hydroxyethoxy) ethyl}-1-piperazinyl]dibenzo[b,f]-[1,4]thiazepine of the Formula I known under the international non-proprietary name quetiapine has anti-dopaminergic and/or serotonin receptor antagonist activity, and is used in the clinical practice as an anti-psychotic or neuroleptic agent especially in the treatment of Schizophrenia.
Quetiapine and its process for preparation is first disclosed in the patent specification EP0240228 and various other processes for the preparation are disclosed in EP0282236, WO0155125, WO9906381, WO2004076431.

In EP0240228, quetiapine was prepared by condensing a compound of Formula II (11-piperazinyldibenzo[b,f][1,4]-thiazepine) with 2-(2-chloroethoxy)ethanol of Formula III in polar organic solvents or aprotic organic solvents, e.g., N.N-dimethylformamide, N-methylpyrrolidone. Polar solvents exemplified were methanol, ethanol, isopropanol or hexanol or their isomers. Compound of Formula II may be employed in the reaction as its free base or its acid addition salt. An inorganic base like sodium carbonate or potassium carbonate was used in the reaction. The reaction was optionally carried out in the presence of promoter/catalyst such as sodium iodide also. The reaction times were reported to be 24 hours or more, but in practice even after 35 hours about 7 to 8% of starting 11-piperazinyldibenzo[b,f][1,4]-thiazepine has been found to be remained unreacted in the reaction. The reaction does not go up to completion, even if excess 2-(2-chloroethoxy)ethanol is used. This incomplete reaction necessitates further purification, incurring heavy losses of product and the purification is difficult due to similar properties of product and starting material 11-piperazinyldibenzo[b,f][1,4]-thiazepine.
A modification of EP0240228 was reported in WO2004076431 which deals with an attempt to reduce the reaction time and in this improved process the 11-piperazinyldibenzo[b,f][1,4]-thiazepine dihydrochloride was reacted with 2-(2-chloroethoxy)ethanol in an organic solvent in presence of a base and a phase transfer catalyst in order to complete reaction in a lesser time. According to the process disclosed in WO2004076431, after 4 hours of reaction unreacted 11-piperazinyldibenzo[b,f][1,4]-thiazepine was found to be about 9.7% (see Example 10). As per the details, the reaction completes only in 17 hours and the product in the reaction mass is only 95.5% and unreacted starting material was 1.1% to 0.26%. WO2004076431 also teaches the use of optional alkali metal halide as a promoter. '431 patent highlights the use of phase transfer catalyst (improved subject matter) for the completion of reaction and the yields reported are still on a lower side ranging from about 60 to 73% (see examples)
This indicates that there is a need for improvement in the process of making quetiapine wherein a complete reaction is achieved that too in much shorter time resulting in high yield and purity.